title: Mummy, A UDP-N-acetylglucosamine pyrophosphorylase, modulates DPP signaling in the embryonic epidermis of Drosophila.
abstract: The evolutionarily conserved JNK/AP-1 (Jun N-terminal kinase/activator protein 1) and BMP (Bone Morphogenetic Protein) signaling cascades are deployed hierarchically to regulate dorsal closure in the fruit fly Drosophila melanogaster. In this developmental context, the JNK/AP-1 signaling cascade transcriptionally activates BMP signaling in leading edge epidermal cells. Here we show that the mummy (mmy) gene product, which is required for dorsal closure, functions as a BMP signaling antagonist. Genetic and biochemical tests of Mmy's role as a BMP-antagonist indicate that its function is independent of AP-1, the transcriptional trigger of BMP signal transduction in leading edge cells. pMAD (phosphorylated Mothers Against Dpp) activity data show the mmy gene product to be a new type of epidermal BMP regulator - one which transforms a BMP ligand from a long- to a short-range signal. mmy codes for the single UDP-N-acetylglucosamine pyrophosphorylase in Drosophila, and its requirement for attenuating epidermal BMP signaling during dorsal closure points to a new role for glycosylation in defining a highly restricted BMP activity field in the fly. These findings add a new dimension to our understanding of mechanisms modulating the BMP signaling gradient.
authors.affiliation: Department of Human Genetics, Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Humphreys
authors.forename: Molly C
authors.initials: MC
authors.lastname: Jud
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Monroe
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Kimball
authors.forename: Matthew
authors.initials: M
authors.lastname: Higley
authors.forename: Danielle
authors.initials: D
authors.lastname: Shipley
authors.forename: Marie Clougherty
authors.initials: MC
authors.lastname: Vrablik
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Bates
authors.forename: Anthea
authors.initials: A
authors.lastname: Letsou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D004789:Enzyme Activation; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006031:Glycosylation; D020935:MAP Kinase Signaling System; D008969:Molecular Sequence Data; D009713:Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism*; D030781:Organisms, Genetically Modified / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D018808:Transcription Factor AP-1; C064196:dpp protein, Drosophila; D009713:Nucleotidyltransferases; C516043:mmy protein, Drosophila
keywords: Dorsal closure; Dpp/BMP/TGF-β signaling; JNK signaling; Raw